發(fā)布時(shí)間：2018-06-13 08:12

  本文選題：杜鵑素 + 氣道炎癥　； 參考：《吉林大學(xué)》2012年博士論文

【摘要】：肺組織是一種非常復(fù)雜的免疫器官，可應(yīng)答多種吸入性的物質(zhì)包括常見的抗原、部分有機(jī)或無機(jī)物、特定種類的感染物或寄生物、氣體及刺激物等，從而引發(fā)氣道阻塞、并伴發(fā)肺間隙、肺泡和支氣管的炎性堵塞。根據(jù)免疫應(yīng)答模式不同將肺部疾病分為固有性肺部免疫應(yīng)答（中性粒細(xì)胞參與的）和適應(yīng)性肺部炎癥應(yīng)答（TH1和TH2淋巴細(xì)胞、嗜酸性粒細(xì)胞等參與的）。本文通過構(gòu)建脂多糖（LPS）誘導(dǎo)的急性肺損傷（固有免疫性肺疾�。┖碗u卵蛋白（OVA）誘導(dǎo)的過敏性哮喘（適應(yīng)性免疫肺疾�。﹥煞N不同的動(dòng)物模型，研究杜鵑素對(duì)不同免疫反應(yīng)引起的氣道炎癥的治療作用及其作用機(jī)制。 急性肺損傷是以彌漫性氣道炎癥為特征的，包括細(xì)胞因子（如TNF-α、IL-6和IL-8）、趨化因子和致炎介質(zhì)等調(diào)節(jié)的中性粒細(xì)胞進(jìn)入間質(zhì)組織的免疫應(yīng)答。過敏性哮喘臨床上是以黏液分泌過盛、氣道堵塞及炎癥、氣道高反應(yīng)性和氣道重塑為特征的慢性炎癥性疾病。過敏性氣道炎癥包括肺組織炎性細(xì)胞浸潤、黏液分泌過多、過敏源特異性IgE增多、Th2型細(xì)胞因子如白細(xì)胞介素4（IL-4）、白細(xì)胞介素5（IL-5）及白細(xì)胞介素13（IL-13）和趨化因子如CCL11和CCL5的表達(dá)增多等。同時(shí)Th1細(xì)胞因子如干擾素γ（IFN-γ）可通過下調(diào)Th2應(yīng)答反應(yīng)抑制過敏性炎癥的發(fā)生。嗜酸性粒細(xì)胞是哮喘發(fā)生時(shí)浸潤到肺組織中的主要炎性細(xì)胞，它與IL-5濃度有關(guān)。對(duì)于炎癥的作用機(jī)制的研究表明，TLR蛋白通過相似的信號(hào)轉(zhuǎn)導(dǎo)通路最終可激活核轉(zhuǎn)錄因子（NF-κB）、激活蛋白（AP-1）、磷脂酰肌醇3激酶（PI3K）和絲裂原蛋白激酶（MAPK）等信號(hào)分子，進(jìn)而在肺部感染性疾病、炎癥和過敏性哮喘中發(fā)揮重要作用。 植物當(dāng)中提取的化合物種類最多且具有抗炎活性的是黃酮類中藥單體，已成為是植物酚的最大組成部分。杜鵑素是一種從杜鵑花中提取出的2,3-二氫-黃酮類化合藥物，已有研究表明，杜鵑素具有抗菌活性，但是沒有關(guān)于其抗炎活性的相關(guān)報(bào)道。 本實(shí)驗(yàn)通過構(gòu)建兩種小鼠的肺疾病模型、評(píng)估了杜鵑素對(duì)過敏性哮喘氣道炎癥和急性肺損傷氣道炎癥的藥理作用，并進(jìn)一步探討其作用機(jī)制。 研究結(jié)果如下： 1.與空白對(duì)照組相比，OVA處理組小鼠肺泡灌洗液中炎性細(xì)胞數(shù)（包括細(xì)胞總數(shù)、嗜酸性粒細(xì)胞數(shù)、中性粒細(xì)胞數(shù)、巨噬細(xì)胞數(shù)和淋巴細(xì)胞數(shù)）等顯著升高。杜鵑素（20和40mg/kg）治療組顯著地抑制了過敏性哮喘肺泡灌洗液中細(xì)胞總數(shù)和嗜酸性粒細(xì)胞數(shù)，對(duì)巨噬細(xì)胞、中性粒細(xì)胞和淋巴細(xì)胞無顯著抑制作用。 2.組織病理學(xué)結(jié)果顯示，OVA處理組小鼠的支氣管和血管周圍出現(xiàn)炎性細(xì)胞浸潤、黏液產(chǎn)物增多以及杯狀細(xì)胞增生等。杜鵑素（20和40mg/kg）治療組顯著地降低了支氣管和血管周圍出現(xiàn)的炎性細(xì)胞浸潤、黏液產(chǎn)物增多以及杯狀細(xì)胞增生等。 3.與空白對(duì)照組相比，OVA處理組哮喘模型組肺泡灌洗液中IFN-γ、IL-10、IL-4、IL-5、IL-13和Eotaxin濃度明顯升高。杜鵑素（20和40mg/kg）治療組可顯著地降低IL-4、IL-5、IL-13和嗜酸性粒細(xì)胞趨化因子的濃度并升高IFN-γ濃度，但是對(duì)IL-10無顯著調(diào)節(jié)作用。此外，杜鵑素（20和40mg/kg）治療組可顯著地降低外周血中OVA-特異性IgE含量。 4.應(yīng)答于不同濃度的乙酰甲膽堿，OVA處理組小鼠可形成氣道高反應(yīng)性，表現(xiàn)為高肺阻力和低肺動(dòng)態(tài)順應(yīng)性。杜鵑素（20和40mg/kg）治療組可顯著的降低肺阻力并升高肺動(dòng)態(tài)順應(yīng)性。 5.與空白對(duì)照組相比，OVA處理組肺組織中趨化因子CCL5和CCL11以及它們的受體CCR1和CCR3基因表達(dá)顯著升高。杜鵑素（20和40mg/kg）治療組可顯著地降低趨化因子極其受體的表達(dá)。 6.杜鵑素可顯著地抑制肺組織中與氣道炎癥和氣道重塑相關(guān)的E-selectin、AMCase、Ym1、Ym2和Muc5ac的mRNA表達(dá)。 7.杜鵑素可顯著地降低由OVA誘導(dǎo)產(chǎn)生的肺組織中p-Akt和p-p70S6K的蛋白的表達(dá)，對(duì)絲裂原蛋白激酶無顯著抑制作用。 8.杜鵑素通過阻斷OVA誘導(dǎo)產(chǎn)生的IκBα降解，抑制IκBα磷酸化，進(jìn)而抑制了NF-κB p65從胞漿轉(zhuǎn)移到核內(nèi)。 9.在體外，杜鵑素可顯著地降低anti-CD3/CD28誘導(dǎo)產(chǎn)生Th2細(xì)胞分泌的IL-4、IL-5和IL-13產(chǎn)物，并可抑制anti-CD3/CD28誘導(dǎo)產(chǎn)生p-Akt、p-p70S6K和p-IκBα的蛋白表達(dá)。 10.低劑量的杜鵑素可協(xié)同低劑量的地塞米松，顯著地抑制OVA誘導(dǎo)的Th2細(xì)胞因子過表達(dá)、炎性細(xì)胞浸潤和肺部病理學(xué)改變。 11.與空白對(duì)照組相比，LPS可顯著升高急性肺損傷肺泡灌洗液中細(xì)胞總數(shù)、中性粒細(xì)胞數(shù)、巨噬細(xì)胞數(shù)以及細(xì)胞因子（TNF-α、IL-6和IL-8）的濃度，，并可上調(diào)NF-κB、p-AKT和MAPKs的蛋白表達(dá)。與地塞米松治療組相比，杜鵑素治療組對(duì)LPS誘導(dǎo)產(chǎn)生的肺損傷癥狀無顯著地抑制作用。 綜上所述，本研究通過采用兩種不同的肺氣道炎癥模型，研究杜鵑素對(duì)不同氣道炎癥的治療作用，首次闡明了杜鵑素對(duì)哮喘性氣道炎癥的抑制作用及其作用機(jī)制，并可協(xié)同糖皮質(zhì)激素類治療過敏性氣道炎癥，為杜鵑素可作為糖皮質(zhì)激素類聯(lián)合用藥用以治療過敏性氣道炎癥提供理論和實(shí)驗(yàn)依據(jù)。
[Abstract]:Lung tissue is a very complex immune organ that respond to a variety of inhalation substances including common antigens, partially organic or inorganic substances, specific types of infection or parasites, gases, and irritants, causing airway obstruction, associated with pulmonary spaces, alveoli and bronchioled clogging. The lungs are different according to the immune response pattern. The disease is divided into intrinsic pulmonary immune response (neutrophilic granulocyte participation) and adaptive pulmonary inflammatory response (TH1 and TH2 lymphocytes, eosinophils). In this paper, an allergic asthma (adaptive immune lung) induced by lipopolysaccharide (LPS) induced acute lung injury (innate immune lung disease) and chicken ovalbumin (OVA) is constructed. Two different animal models were used to study the therapeutic effect of rhododendrin on airway inflammation induced by different immune responses and its mechanism.
Acute lung injury is characterized by diffuse airway inflammation, including cytokines (such as TNF- alpha, IL-6 and IL-8), chemokines and inflammatory mediators that regulate the immune response of neutrophils into interstitial tissue. Allergic asthma is characterized by mucus secretion, airway plugging and inflammation, airway hyperresponsiveness, and airway remodeling. Chronic inflammatory diseases. Allergic airway inflammation includes inflammatory cell infiltration of the lung tissue, excessive mucus secretion, anaphylactic specific IgE, Th2 cytokines such as interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 13 (IL-13), and chemokine such as CCL11 and CCL5, such as Th1 cell factors such as interference. IFN- gamma can inhibit the occurrence of anaphylactic inflammation by down regulation of the Th2 response. Eosinophils are the main inflammatory cells infiltrating into the lung tissue during the occurrence of asthma. It is related to the concentration of IL-5. The study of the mechanism of the action of inflammation indicates that the TLR protein can eventually activate the nuclear transcription factor (NF- kappa B) through similar signal transduction pathways. Activated protein (AP-1), phosphatidylinositol 3 kinase (PI3K) and mitogen kinase (MAPK) signal molecules, and thus play an important role in pulmonary infectious diseases, inflammation and allergic asthma.
The most species and anti-inflammatory activity of the compounds are flavonoids, which are the largest component of the plant phenols. The azalein is a 2,3- two hydrogen flavone compound extracted from the Rhododendron. The studies have shown that rhododendrin has anti - bacterial activity but no anti - inflammatory activity. Close the report.
In this experiment, the pharmacological effects of Rhododendron on airway inflammation in allergic asthma and airway inflammation in acute lung injury were evaluated by constructing two models of lung disease in mice, and the mechanism of its action was further explored.
The results of the study are as follows:
1. compared with the blank control group, the number of inflammatory cells in the alveolar lavage fluid (including the number of cells, eosinophils, neutrophils, number of macrophages, and the number of lymphocytes) in the OVA treatment group were significantly increased. The total number of cells and the eosinophils in the alveolar lavage fluid of the allergic asthma were significantly inhibited by the azalein (20 and 40mg/kg) treatment group. The number of cells had no significant inhibitory effect on macrophages, neutrophils and lymphocytes.
2. the results of histopathology showed that inflammatory cells infiltrated, mucus products and goblet cells proliferated around the bronchi and blood vessels of the OVA treatment group. The treatment group of rhododendrin (20 and 40mg/kg) significantly reduced inflammatory cell infiltration, increased mucous products and goblet cell proliferation around the bronchi and blood vessels.
3. compared with the blank control group, the concentration of IFN- gamma, IL-10, IL-4, IL-5, IL-13 and Eotaxin in the alveolar lavage fluid of the OVA treatment group was significantly increased. The concentration of IL-4, IL-5, IL-13 and eosinophil chemotactic factors and the increase of IFN- gamma concentration were significantly reduced in the treatment group of azalein (20 and 40mg/kg), but there was no significant regulation on the concentration of IFN- gamma. In addition, rhododendrin (20 and 40mg/kg) treatment group could significantly reduce OVA- specific IgE content in peripheral blood.
4. in response to different concentrations of methacholine, OVA treated mice could form airway hyperresponsiveness, showing high lung resistance and low lung dynamic compliance. The treatment group of azalein (20 and 40mg/kg) could significantly reduce lung resistance and increase lung dynamic compliance.
5. compared with the blank control group, the expression of chemokine CCL5 and CCL11, and their receptor CCR1 and CCR3 genes in the lung tissue of the OVA treatment group were significantly increased. The expression of chemokine and extreme receptors could be significantly reduced by the azalein (20 and 40mg/kg) treatment groups.
6. rhododendrin significantly inhibited the expression of E-selectin, AMCase, Ym1, Ym2 and Muc5ac in lung tissue associated with airway inflammation and airway remodeling.
7. rhododendrin significantly decreased the expression of p-Akt and p-p70S6K in lung tissue induced by OVA, and had no significant inhibitory effect on mitogen activated protein kinase.
8. rhododendrin inhibited the degradation of I kappa B alpha induced by OVA and inhibited the phosphorylation of I kappa B alpha, thereby inhibiting the transfer of NF- B p65 from cytoplasm to the nucleus.
9. in vitro, rhododendrin can significantly reduce anti-CD3/CD28 induced IL-4, IL-5 and IL-13 products produced by Th2 cells, and inhibit the expression of p-Akt, p-p70S6K and p-I kappa B alpha induced by anti-CD3/CD28.
10. the low dose of rhododendrin can be combined with low dose of dexamethasone, which significantly inhibits the overexpression of Th2 cytokines induced by OVA, infiltration of inflammatory cells and pathological changes in the lungs.
11. compared with the blank control group, LPS could significantly increase the total number of cells, the number of neutrophils, the number of macrophages and the concentrations of cytokines (TNF-, IL-6 and IL-8) in the alveolar lavage fluid of acute lung injury, and up regulation of the protein expression of NF- kappa B, p-AKT and MAPKs. Compared with the dexamethasone treatment group, the lung damage induced by the rhododenin treatment group was induced by LPS. The symptoms of injury had no significant inhibitory effect.
To sum up, we studied the therapeutic effect of Rhododendron on different airway inflammation by using two different pulmonary airway inflammation models. It was the first time to elucidate the inhibitory effect of Rhododendron on asthmatic airway inflammation and its mechanism. It can be used in the treatment of allergic airway inflammation with glucocorticoid, and the rhododendrin can be used as glucocorticoid. Combined drug use provides theoretical and experimental evidence for the treatment of allergic airway inflammation.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R562.25

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 陸光潤,柳廣南,鐘小寧,鄧靜敏,蘇紅,許輝;慢性阻塞性肺疾病腫瘤壞死因子的檢測意義[J];廣西醫(yī)科大學(xué)學(xué)報(bào);1999年03期

2 張中橋;治療哮喘應(yīng)著重控制氣道炎癥反應(yīng)[J];中華醫(yī)學(xué)信息導(dǎo)報(bào);2000年12期

3 賀連坤,金高娃,馬利;輕度哮喘病人吸煙與氣道炎癥的關(guān)系(附30例報(bào)告)[J];醫(yī)學(xué)理論與實(shí)踐;2002年10期

4 羅煒,賴克方,鐘南山;誘導(dǎo)痰檢測的方法學(xué)及其在氣道炎癥評(píng)價(jià)中的應(yīng)用[J];國外醫(yī)學(xué).呼吸系統(tǒng)分冊(cè);2004年06期

5 徐少華,王偉,王暉,張穎,畢少杰;全身短期應(yīng)用糖皮質(zhì)激素治療加重期慢性阻塞性肺疾病氣道炎性細(xì)胞因子的產(chǎn)生[J];現(xiàn)代免疫學(xué);2005年04期

6 王力寧;鐘華;;中醫(yī)藥對(duì)哮喘氣道炎癥防治研究概況[J];四川中醫(yī);2006年06期

7 張穎;李廷謙;;白介素-17與呼吸系統(tǒng)疾病研究進(jìn)展[J];國際呼吸雜志;2006年10期

8 歐陽秋星;;哮喘嚴(yán)重程度與血清特異性IgE的關(guān)系分析[J];現(xiàn)代醫(yī)院;2008年02期

9 喻寧芬;喻寧芳;鄧禮;于力;翁志媛;陳英;肖雪;張又祥;李書華;;磷酸酰肌醇-3激酶抑制劑對(duì)小鼠氣道炎癥影響的實(shí)驗(yàn)研究[J];現(xiàn)代醫(yī)院;2008年04期

10 齊金萍;方秀斌;;抗SH2-Bβ抗體可減輕哮喘小鼠氣道炎癥和氣道高反應(yīng)性[J];中國免疫學(xué)雜志;2009年06期

相關(guān)會(huì)議論文 前10條

1 鄒外龍;;誘導(dǎo)痰技術(shù)及其在評(píng)價(jià)氣道炎癥中的進(jìn)展[A];第二十三屆航天醫(yī)學(xué)年會(huì)暨第六屆航天護(hù)理年會(huì)論文匯編[C];2007年

2 謝強(qiáng)敏;趙曉燕;陳季強(qiáng);卞如濂;;母牛分枝桿菌菌苗對(duì)氣道炎癥和高反應(yīng)性以及細(xì)胞因子分泌的影響[A];中國藥理學(xué)會(huì)第八次全國代表大會(huì)暨全國藥理學(xué)術(shù)會(huì)議論文摘要匯編[C];2002年

3 歐陽海峰;吳昌歸;;外源性骨髓間充質(zhì)干細(xì)胞對(duì)哮喘小鼠氣道炎癥的抑制作用[A];中華醫(yī)學(xué)會(huì)第七屆全國哮喘學(xué)術(shù)會(huì)議暨中國哮喘聯(lián)盟第三次大會(huì)論文匯編[C];2010年

4 張固琴;聶漢祥;楊炯;;硫酸腦苷酯對(duì)哮喘小鼠過敏性氣道炎癥的影響[A];中華醫(yī)學(xué)會(huì)第七屆全國哮喘學(xué)術(shù)會(huì)議暨中國哮喘聯(lián)盟第三次大會(huì)論文匯編[C];2010年

5 劉艷明;農(nóng)光民;李樹全;;布地奈德早期干預(yù)對(duì)對(duì)哮喘小鼠氣道炎癥和IL-6/STAT3信號(hào)通路的影響[A];中華醫(yī)學(xué)會(huì)第十五次全國兒科學(xué)術(shù)大會(huì)論文匯編（上冊(cè)）[C];2010年

6 趙瑩;孔靈菲;;誘導(dǎo)痰在支氣管哮喘氣道炎癥評(píng)價(jià)中的應(yīng)用[A];中華醫(yī)學(xué)會(huì)第五次全國哮喘學(xué)術(shù)會(huì)議暨中國哮喘聯(lián)盟第一次大會(huì)論文匯編[C];2006年

7 于瑩瑩;吳輝;宋宏;;交通主干道尾氣污染對(duì)大鼠的氣道損傷的現(xiàn)場研究[A];中國環(huán)境科學(xué)學(xué)會(huì)2009年學(xué)術(shù)年會(huì)論文集（第四卷）[C];2009年

8 彭秋鳳;孔靈菲;;咳嗽變異性哮喘患者誘導(dǎo)痰NGF和IL-4水平及氣道炎癥特征的探討[A];中華醫(yī)學(xué)會(huì)第七屆全國哮喘學(xué)術(shù)會(huì)議暨中國哮喘聯(lián)盟第三次大會(huì)論文匯編[C];2010年

9 李昌崇;鄭吉善;蘇苗賞;張維溪;羅運(yùn)春;李孟榮;董琳;陳小芳;蔡曉紅;張正霞;;胸腺活化調(diào)節(jié)趨化因子及其受體CCR4在哮喘小鼠氣道炎癥中的作用[A];2006（第三屆）江浙滬兒科學(xué)術(shù)會(huì)議暨浙江省兒科學(xué)術(shù)年會(huì)論文匯編[C];2006年

10 何勝東;賴克方;姚衛(wèi)民;羅煒;鐘南山;;卡介苗核酸及多糖組分對(duì)支氣管哮喘小鼠氣道反應(yīng)性及氣道炎癥的作用[A];中華醫(yī)學(xué)會(huì)第七次全國呼吸病學(xué)術(shù)會(huì)議暨學(xué)習(xí)班論文匯編[C];2006年

相關(guān)重要報(bào)紙文章 前10條

1 柏京;控制氣道炎癥很關(guān)鍵[N];大眾衛(wèi)生報(bào);2009年

2 高國起;監(jiān)測哮喘兒氣道炎癥變化有新指標(biāo)[N];中國醫(yī)藥報(bào);2002年

3 胡德榮;上海瑞金醫(yī)院揭示哮喘氣道炎癥中的抗炎新機(jī)制[N];中國醫(yī)藥報(bào);2007年

4 高國起 王省;監(jiān)測哮喘患兒氣道炎癥又有新突破[N];科技日?qǐng)?bào);2003年

5 記者 黃才剛;慢性氣道炎與細(xì)胞因子失衡有關(guān)[N];健康報(bào);2000年

6 李天舒邋通訊員 汪敏;哮喘免疫抗炎新機(jī)制被發(fā)現(xiàn)[N];健康報(bào);2007年

7 本報(bào)記者 李薇;哮喘病人宜小勞[N];醫(yī)藥養(yǎng)生保健報(bào);2006年

8 車海亮;幾種中藥復(fù)方祛痰藥[N];醫(yī)藥養(yǎng)生保健報(bào);2006年

9 劉長山 劉道安 孫曉軍;控制哮喘 快樂生活[N];健康報(bào);2006年

10 北京大學(xué)人民醫(yī)院呼吸內(nèi)科主任 何權(quán)瀛;“三位一體”防控哮喘[N];光明日?qǐng)?bào);2007年

相關(guān)博士學(xué)位論文 前10條

1 彭娟;白介素23調(diào)節(jié)過敏性氣道炎癥的機(jī)制研究[D];武漢大學(xué);2010年

2 黃勇;氣道粘蛋白大分子末端唾液酸化對(duì)粘蛋白—銅綠假單胞菌相互作用的影響及其機(jī)制[D];第三軍醫(yī)大學(xué);2006年

3 孔凡盛;穴位敷貼治療被動(dòng)吸煙大鼠氣道炎癥機(jī)制的研究[D];廣州中醫(yī)藥大學(xué);2008年

4 潘豐滿;止哮平喘方對(duì)哮喘大鼠嗜酸性粒細(xì)胞凋亡及調(diào)控基因表達(dá)的影響[D];湖北中醫(yī)學(xué)院;2009年

5 杜強(qiáng);黃芪甲苷對(duì)慢性哮喘模型小鼠氣道炎癥和氣道重塑的影響以及機(jī)制探討[D];南京醫(yī)科大學(xué);2009年

6 于化鵬;過敏性哮喘中Eotaxin及CCR3致氣道炎癥機(jī)制的研究[D];第四軍醫(yī)大學(xué);2001年

7 李琦;過氧化物酶體增殖物激活受體γ與支氣管哮喘關(guān)系的研究[D];吉林大學(xué);2007年

8 靳英麗;神經(jīng)生長因子在支氣管哮喘發(fā)病中的作用研究[D];吉林大學(xué);2008年

9 胡斯明;調(diào)節(jié)性T細(xì)胞與Th17細(xì)胞在支氣管哮喘中失衡表達(dá)的實(shí)驗(yàn)研究[D];南方醫(yī)科大學(xué);2009年

10 賀淼;大氣污染顆粒物對(duì)卵蛋白誘導(dǎo)的哮喘小鼠氣道炎癥的作用及其機(jī)制研究[D];中國醫(yī)科大學(xué);2010年

相關(guān)碩士學(xué)位論文 前10條

1 楊雪梅;慢性阻塞性肺疾病大鼠模型肺內(nèi)白介素-9和干擾素-γ的表達(dá)及其與氣道炎癥的關(guān)系[D];蘭州大學(xué);2006年

2 呂小琴;藍(lán)桉油對(duì)大鼠慢性氣道炎癥及粘蛋白高分泌的影響[D];浙江大學(xué);2004年

3 吳茱萸;慢性阻塞性肺疾病患者血清中單核細(xì)胞趨化蛋白-1、轉(zhuǎn)化生長因子-β水平及意義[D];鄭州大學(xué);2005年

4 盧獻(xiàn)靈;慢性阻塞性肺疾病（COPD）大鼠肺組織腺苷A1受體的表達(dá)及糖皮質(zhì)激素、抗膽堿藥的干預(yù)作用[D];四川大學(xué);2004年

5 戴斌;COPD患者可溶性髓樣細(xì)胞表達(dá)的激發(fā)受體-1的測定及其意義[D];廣西醫(yī)科大學(xué);2007年

6 許小揚(yáng);哮喘豚鼠MMP-9、TIMP-1的表達(dá)及與氣道炎癥及重塑的關(guān)系[D];中國醫(yī)科大學(xué);2002年

7 王妍;煙曲霉菌孢子致哮喘大鼠肺病理生理學(xué)的改變[D];上海交通大學(xué);2007年

8 時(shí)翠芹;辣椒素咳嗽敏感性及氣道炎癥測定在慢性咳嗽中的意義[D];同濟(jì)大學(xué);2007年

9 鄭曉晶;NGF對(duì)支氣管哮喘大鼠氣道炎癥的影響及作用機(jī)制的研究[D];重慶醫(yī)科大學(xué);2008年

10 李莉芳;噻托溴銨對(duì)慢性阻塞性肺疾病大鼠氣道炎癥和重塑作用的研究[D];山西醫(yī)科大學(xué);2008年

本文編號(hào)：2013333